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Andrea Richardson, MD, PhD

Associate Professor of Pathology
Director, Pathology and Breast Pathology,
Johns Hopkins Capitol Region
Johns Hopkins University School of Medicine
Baltimore, Maryland

Current Research

Goal: To determine which breast cancer patients will respond to certain treatments.

Impact: Dr. Richardson is conducting studies aimed at identifying breast tumors that share common features with BRCA-driven breast cancers and thus could potentially be treated with DNA-damaging drugs such as PARP inhibitors. Her findings may be used to predict which treatment will work best for an individual patient’s tumor.

What’s next: In addition to continuing their current investigation, Dr. Richardson and her team will establish a biorepository that allows them to study biomarkers of response to therapy in lobular breast cancer.   

Breast cancers that are driven by mutations in the BRCA1 and BRCA2 genes have a defect in how the cells repair DNA damage. This defect makes them responsive to treatments such as PARP inhibitors, a newer class of anti-cancer drugs. But there are also some breast cancers with mutations in other DNA repair pathway genes that have features similar to those of BRCA tumors, and they may also respond to PARP inhibitors. Dr. Richardson’s work is focused on discovering these other mutations so that breast cancer patients who have them can be identified and benefit from treatment with PARP inhibitors and other DNA-damaging drugs.

Full Research Summary

Research area: Overcoming resistance to targeted therapies and improving outcomes in patients with aggressive breast cancers.

Impact: BRCA-driven breast cancers have a distinctive feature associated with defects in DNA repair. This leads to genomic instability – frequent DNA damage events – that makes tumors very aggressive. While this feature makes the tumor cells very mutable and thus adaptable , it also makes them vulnerable to a class of drugs called PARP inhibitors as well as other DNA damaging agents, because the cells cannot repair the DNA damage cause by the drug. Unfortunately, tumors develop resistance to these drugs by activating alternative DNA repair pathways. Dr. Richardon’s research is focused on understanding how these compensatory pathways work and to determine whether mutations in other genes involved in DNA repair may be targets for PARP inhibitors. Ultimately, these studies will help inform the selection of the most effective treatments for patients with BRCA-driven cancers.

Current investigation: Dr. Richardson and her colleagues are conducting laboratory studies to understand how loss of BRCA genes leads to genomic instability. They are also exploring the mechanism of action of other DNA repair pathways that tumor cells may use to compensate for BRCA loss in order to identify strategies to prevent resistance to PARP inhibitors or other DNA damaging drugs.

What she’s learned so far: She and her team have shown that patients with tumor mutations in some but not all DNA repair pathway genes share many features with BRCA-driven tumors and may also benefit from treatment with PARP inhibitors.

What’s next: Dr. Richardson will continue this work with a specific focus on identifying mechanisms of resistance to DNA damaging agents in triple negative breast cancer.

Biography

Dr. Andrea L. Richardson is an Associate Professor of Pathology and Director of the Pathology Community Practice Division at Johns Hopkins University School of Medicine, where she moved in 2015 after more than eight years on the faculty of Brigham and Women's Hospital, Harvard Medical School in Boston. She maintains an active clinical practice on the breast pathology consultation service. Her research focus is breast cancer genetics and pathobiology. She is actively engaged in translational breast cancer research, frequently with multi-disciplinary teams. Dr. Richardson has extensive experience in tissue-based molecular assays. Her laboratory research has focused on characterizing the molecular aberrations in subtypes of breast cancer important for pathogenesis, tumor progression, and tumor response to therapy.

Large Researcher Headshot - Richardson Andrea

BCRF Investigator Since

2007

Area(s) of Focus